Simultaneous determination of midazolam and 1'-hydroxymidazolam in human plasma by liquid chromatography with tandem mass spectrometry |
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Authors: | Li Wenkui Luo Suyi Smith Harold T Tse Francis L S |
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Affiliation: | Department of Drug Metabolism and Pharmacokinetics, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. Wenkui.li@novartis.com |
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Abstract: | A sensitive and simple liquid chromatography-tandem mass spectrometry method for the determination of midazolam and 1'-hydroxymidazolam in human plasma has been developed and validated with a dynamic range of 0.1-250 ng/mL. The analysis was based on semi-automated liquid-liquid extraction followed by evaporation of the extraction solvent, reconstitution and chromatography on a reversed-phase C(18) column. The mobile phase consists of 5 mm ammonium acetate and methanol and runs in gradient at a flow rate of 0.25 mL/min with column temperature of approximately 20 degrees C. The entire column effluent was transferred into the LC-MS/MS interface operated in positive electrospray ionization mode. The chromatographic run time was 4.3 min per injection, with retention times for midazolam, 1'-hydroxymidazolaml and the internal standard, triazolam, of 2.5, 2.3 and 2.1 min, respectively. The intra-day and inter-day precision (RSD %) and accuracy (bias %) of the quality control samples were <15.0% and within +/-13%, respectively. The current method has been applied to a clinical drug-drug interaction study in human. |
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Keywords: | midazolam 1′‐hydroxymidazolam triazolam LC‐MS/MS human plasma semi‐automation drug–drug interaction |
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